Kojic Acid as a Natural Hypopigmenting Agent: Biological Activities, Delivery Challenges, and Nanotechnology-Based Strategies.

Hyperpigmentation is a multifaceted process that involves the overproduction and uneven distribution of melanin. The number of patients with skin hyperpigmentation is on the rise, representing the most common complaint in dermatology clinics. Treatment focuses mainly on melanocyte reduction and stopping melanosome production due to their expected degradative effects. Kojic acid (KA), a widely known natural depigmenting agent of fungal origin, acts by inhibiting the action of tyrosinase, the enzyme that catalyzes melanin production. Although it has been used for many years in skin-lightening preparations, kojic acid suffers from many problems that reduce its efficacy, including poor chemical stability, hydrophilicity, and adverse effects. Many modern systems like polymeric, lipidic, and inorganic nanocarriers have been used to provide controlled release, improve the delivery of kojic acid to the target site of action, and provide protection during storage. Consequently, the aim of this narrative review is to present the current literature reports concerning the biological activity of kojic acid, with particular emphasis on recent advances in nanotechnology-based delivery systems, including lipidic, vesicular, polymeric, inorganic, and other emerging nanocarriers developed for pharmaceutical and cosmetic applications. This review also introduces prospective, next-generation delivery strategies that remain unaddressed in the current literature, which may optimize the therapeutic efficacy of kojic acid. It also reports the main challenges that face the use of nanoparticles for kojic acid delivery, namely, the lack of clinical validation, limited safety data, and large-scale production reproducibility, as well as regulatory constraints, thereby identifying key research gaps and future priorities that necessitate the prioritization of clinical evaluation of kojic acid delivery systems.